The newest research about living with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (ME/CFS)/fibromyalgia, with personal observations
(the most pertinent parts of long articles will be highlighted for the reader)

About The Author

On March 4, 1988, I was diagnosed with Post-Viral Syndrome, which CDC soon decreed had to be referred to by the silly name "Chronic Fatigue Syndrome". My symptoms definitely traced back to a severe flu-like illness with a 105 fever for several days in mid-February 1987.
Despite relapses and increasing symptoms, I continued to work full-time as a legal secretary/paralegal -- even when I had no Quality of Life because I had to spend every non-working hour in bed so I could work the next day -- until February 2000, when months of severe sleep disturbance and ever-increasing symptoms (due to sleeping 2 hours or less a night due to the pain) cost me my job.
The doctors and judge didn't want to hear about failed attempts to return to work; they just assumed I don't want to work. "Don't confuse me with facts, my mind is already made up."
Since ADA will not force an employer to provide the accommodations I need, I started my own business so I could lie down whenever I needed to. I do proofreading and editing from home.
Visit www.CFSfacts.org or CFS Facts at YahooGroups or on Facebook if you want to learn the truth behind the myths.

Saturday, December 26, 2015

In a talk covering his virus hunting career, the threat of pathogens to humanity, and his work with chronic fatigue syndrome (ME/CFS), he dropped a bombshell: he stated that he believes it's possible to solve ME/CFS in three to five years.

Called the top virus hunter in the world, Ian Lipkin runs the Center for Infection and Immunity at Columbia, and is the director of the Center for Research in Diagnostics and Discovery (CRDD) at the NIH. He also worked closely with Steven Soderbergh on his film Contagion.

Likpin cited the findings of their work to date.

The suspected pathogens don't appear to be the problem (the CII is reportedly looking further at herpesviruses.)

Evidence suggests altered microbiomes (gut flora) are present

Striking differences in immune expression between shorter and longer duration patients appear to be present

Preliminary evidence suggests that levels "X" and "Y" metabolites and, at least, one immune protein are significantly altered in ME/CFS. (Lipkin embargoed this information pending publication of the paper. One of them is highly unusual.)

Lipkin emphasized, though, that ME/CFS is not a one-size fits all disease. For instance, it's possible that fungi may be a problem for some patients. That's an intriguing idea given the recent fungi funding in Alzheimer's disease published in Nature.

Then Lipkin made his bold declaration "We're going to solve this in three to five years", with a big proviso.Provided the resources are made available,he believes science can crack ME/CFS fairly quickly.

Lipkin was at the event to support the Simmaron Research Institute's next spinal fluid study. The results of the first one – the most extensive spinal fluid study ever done in ME/CFS – were eye-opening. A comparison to multiple sclerosis (MS) found evidence of immune dysregulation almost equal to that found in MS. The difference was that instead of being raised, the cytokine levels were reduced in ME/CFS.

That finding surely left a big smile on Lipkin's and Hornig's faces. Earlier they had found evidence of a profound reduction in immune functioning in the blood of later-duration ME/CFS patients. Now a similar reduction was found in their spinal fluid. Having findings in two different systems match has rarely happened in ME/CFS. That suggested they were uncovering system-wide problems.

No wonder Lipkin was eager to begin a new and larger spinal fluid study. It's part of achieving his bucket list.

- See more at: http://simmaronresearch.com/2015/12/ian-lipkin-three-to-five-years-to-solve-chronic-fatigue-syndrome-mecfs/#sthash.FI5MX1L9.dpuf

Sunday, December 13, 2015

neuroscientist Professor Chris Chambers of Cardiff University, whotweeted, "If @KingsCollegeLon is seeking to do itself 'reputational damage', hiding trial data shd do the job", and leading University of Virginia research psychologist Brian Nosek, whotweeted, "King's College data sharing refusal and rationale are antithetical to science". Dr Nosek is the Executive Director of theCenter for Open Science.

It is possible to leavecommentson the PLOS ONE site in relation to the PACE paper. Professor Coyne has posted a comment about the study authors' refusal to share their data and in response, one patient wrote, "Patients are relying on PLOS One to be the first scientific institution to stand up for good scientific practice in the context of the PACE trial… Patients don't risk their health in clinical trials so that study authors can misrepresent the results and prevent independent researchers from investigating them."

I was privileged to attend the 10th Invest in ME conference in Londonon 29th May 2015 following on from the 2-day colloquium attended by 60invited delegates from around the world.

Participants from 17 countries were welcomed to the conference openingby Invest in ME and the chair was then taken by Dr Ian Gibson.

The keynote speech was given by Professor Ian Charles (Norwich, UK).He has recently been appointed by the Institute of Food Research tolead the programme to develop the UK's new centre for Food and Healthbased at Norwich Research Park. This is a large complex incorporating:The Institute of Food Research, The University of East Anglia, theNorfolk and Norwich University Hospital and the Genome AnalysisCentre. There will be interdisciplinary approaches to address manycomplex problems.

He discussed the gut microbiome, explaining that we have ten timesmore bacteria than cells. He asked the questions: "Do alterations inintestinal barrier integrity and microbiota exist in ME?" and "Isthere evidence of immune exposure and reactivity to commensal microbesin ME patients?" He will be working within an interdisciplinary model,which will become an international hub for food and health research,with top class scientists appointed. Many departments will be workingtogether.

This new approach will be holistic, systematic and integrated todeliver faster innovation. It will be a site of excellence and willliaise with government. The aim is to lead to personalized nutritionto benefit the individual microbiome.

The first presentation was given by Mady Hornig (Columbia, USA). Shediscussed markers of immunity and metabolism in ME. She described a3-strikes hypothesis regarding development of the illness, involvinggenes, environment and timing. These affect brain outcomes, and shediscussed the effects of the mother's own immune system on thedeveloping foetal brain. Her cytokine profile could be implicated inthe risks of the infant developing nervous system disorders, evenyears later. The microbiome of the mother also influences theoffspring's immune system with potential risks. Many disorders of thenervous system may stem from immune-mediated pathogenesis.

She then described how there is an increase in plasma levels ofpro-inflammatory cytokines associated with recent illness in ME, andas the illness progresses, these levels fall. A striking finding isthe very high level of IFN-gamma in short duration illness. It ispossible that different cytokine profiles may affect the potentialbenefit of different types of therapies. Therapies may need to bedifferent at different stages of the illness.

Looking at the cerebrospinal fluid (CSF) comparing ME, MS andcontrols, there were some similarities between ME and MS but thecontrols had very different immune signatures. The patterns of immunemolecules in the CSF of ME subjects, who largely had been ill for manyyears, were similar to those Invest in ME

Discussing metabolomics, she then described 7 classes of 180metabolites. Alterations were found in a wide range of metabolites inME, including ADMA, which is associated with nitrosative stress, andin tryptophan and serotonin. These metabolomic changes were found tobe correlated with changes in cytokines.

In the gut, there may be imbalances due to foods leading to bacterialfermentation. Probiotics and faecal transfers do have potential, ashave been found to prevent encephalopathy in cirrhosis of the liver.

A question was asked as to whether the effects of SSRIs may beaffected by the serotonin levels and whether the duration of theillness could be implicated here. It may be that patients will need tobe categorized according to illness duration, and there may be asubgroup who will respond. But serotonin levels are not the onlymechanism. It is likely to be more complex than that.

Jonas Berquist (Uppsala, Sweden) describing himself as an analyticalchemist, discussed the Proteomics in ME/CFS. The first ever analyticalchemist was Tobern Olaf Bergman from Sweden. So there is a strongSwedish tradition in this field. Berquist's lab does general researchand uses mass spectrometry looking at endogenous analytes. Hedescribed proteomics as life's molecular machines – i.e. proteinswhich carry out all functions of the body.

He looked at when, where, how proteins are expressed.Post-translational modifications (PTMs) occur. This can be measuredusing 3D gel electrophoresis, but nowadays "shotgun" proteomics isused to separate them out. Many instruments are used and some of themare very big machines, using high resolution mass spectrometry. It isimportant to use the correct samples from serum and tissues. The testsare extremely sensitive. He compared the small concentrationsmeasurable with these techniques as the amount found if a cup ofcoffee is poured into a swimming pool.

When looking at the CSF, the total volume is about 150ml and 5-600mldaily is produced. Sample handling needs to be extremely careful. Hislabs have produced a 776 page list of the peptides in the CSF. Thereare different ranges with overlaps in different conditions. The studygives meaningful insights into the biological processes in ME/CFS.There are significantly changed proteins involved in neurologic,metabolic and immune diseases. He has looked at upstream anddownstream analysis.

The conclusion is that this work could lead to biomarkers, which maybediagnostic, prognostic and therapeutic.

Luis Nacul (London, UK) reviewed the epidemiological evidence onME/CFS looking at the current status and implications for research andservice delivery. He described it as a jigsaw coming together. He feltthat the symptoms of encephalitis were very similar to the symptoms ofME, which MAY therefore BE indicative of neuro-inflammation. He saidthat the diagnosis of ME SHOULD BE DISTINGUISHED FROM THAT OF ChronicFatigue Syndrome, AS usually the term ME was indicative of moresymptoms. He mentioned a variance in prevalence rates, with femalesmore commonly affected than males. Overall population estimates arebetween 0.1% and 0.7%. Young adulthood is the commonest age ofincidence. In patients with ME/CFS, activity is significantlydiminished. He stressed that we need to look at specificity andsensitivity, and risk ratio and risk difference. Specificity shouldtake precedence over sensitivity for validity.

The NICE guidelines ON MANAGEMENT were mentioned. There are LIMITEDeffects shown in the clinical response to CBT. But the results may notbe valid as STUDIES USED IN THE META- ANALYSES ARE OF POOR QUALITY ANDA LARGE PROPORTION patients DID not complete a trial, and thereforeresults may not be valid. It could be described as an additional"coping" therapy, WHICH SHOULD NOT DISTRACT US FROM FINDING SPECIFICTREATMENTS FOR ME. Invest in ME

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We need to concentrate on biomarkers for the future, with casestratification and intervention strategies. The current UK biobank has500 participants, with 17,000 aliquots stored as of March 2015.

Amolak Bansal (Surrey, UK) gave an overview of the diagnosis anddifferential diagnosis on ME. He explained how fatigue occurs in manyillnesses, but is the cardinal feature of ME/CFS. He said thepost-exertional malaise is hard to explain. He then went through thevarious criteria being used to diagnose the illness. He discussed thedifferences between the criteria (CDC, ICC etc.). He thinks that theterm SEID may be too simple. He talked of exclusion criteria,including temporary exclusion criteria, such as hypothyroidism andmorbid obesity leading to sleep apnoea; and psychiatric exclusioncriteria. He mentioned comparisons which are made between the termsCFS and ME.

He then went through the Sutton scoring system developed at hisclinic. The main symptoms have a "loaded" score: e.g. PEM scores 3points, sleep problems 2 and all other symptoms 1 point. 8 or morepoints out of 13 points is needed for a diagnosis. All patients musthave post exertional malaise. For subjects involved in research heuses a score of 10+ from 13 to ensure a critically well-definedpopulation. Subjects with a significant depression or anxiety areexcluded from research but can still be diagnosed with ME/CFS formanagement purposes if they have sufficient points and the depressionand anxiety is secondary to the ME/CFS. Treating the depression,anxiety and ME/CFS are all critical to improvement in these people. Itis important to note that sensitivity to medication, and alcoholintolerance are very common in ME/CFS. Fewer than 10% patients cantolerate alcohol. Another unusual sign in 60 % patients is alteredpupillary reflexes (alternating dilatation and contraction while alight is shined) and sighing respirations. Other physical signsinclude: joint hypermobility (20%), increased respiratory rate (80%),coldness of peripheries (70%). Conditions that can cause symptomssimilar to ME/CFS include: hypothyroidism, Addison's disease,pituitary dysfunction, Sjogren's syndrome, gluten sensitivity,persistent anxiety, primary sleep disorder, Ehlers Danlos Syndromejoint/hypermobility type, cardiac dysfunction, Parkinson's disease andtemporo-mandibular joint disorder.

He then compared ME/CFS with depression and anxiety. The sleepdisturbance in ME/CFS is different to that in depression and theformer are also markedly hypersensitive to psychoactive medications.Functionally those with ME/CFS can start a task, but then trenddownwards while those with depression cannot start a task as they havereduced motivation, but once started they can often manage to completeit. Those with ME/CFS rarely resort to alcohol, while those withdepression do frequently. However chronic anxiety associated withME/CFS will deplete energy further, contribute to faintness, cognitivedifficulties and increased respiration.

He then talked about appropriate investigations. The basic bloodworkup should be done as for all fatiguing illnesses and these aresufficient to exclude other causes for chronic fatigue in the majorityof patients. Things to add in depending on history and symptoms maybe: ANA, CK, calcium, magnesium, tests for Addisons and on rareoccasions infection serology (Lyme, viral) and neurologicalabnormalities (MRI, fMRI, PET scans). Other tests that areoccasionally considered include tilt table, ECG monitoring andneuropsychological tests. Unfortunately in the UK searching fortriggering infections, such as viral, bacterial (incl spirochaetes),protozoa and fungi (no evidence for involvement of candida) is rarelyrewarding in terms of offering specific therapeutic options. Historyof immunisations on rare occasions may suggest a possible trigger andthere is recent controversy about the HPV vaccine.

Quite often it is a difficult question of how far to delve into issuessuch as life events, stress, physical injuries, environmental toxinsand childhood trauma as there is at least some evidence that they mayall play a cofactor role in precipitating ME/CFS. He then discussedthe importance of the control population in ongoing ME/CFS Invest inME

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research. Although the ideal control group would be family membersthis is often difficult and perhaps monitoring people with ME/CFSthrough several periods of relapse and remission would be best wayforward.

Sonya Marshall-Gradisnik and Don Staines (Griffith University, GoldCoast, Australia) presented their work on biomarkers in ME/CFS. Theyhad had two recent papers published –

The two researchers highlighted these papers are from a series ofpapers that will be released in the coming months.

These two papers discussed this important work on single nucleotidepolymorphisms (SNPs) in both transient receptor potential (TRP) ionchannel genes and acetylcholine (AChR) receptor genes. TRP and AChRare part of the ancient or innate immune system. The TRP ion channelsrespond to environmental threats, temperature, chemicals etc. They aredistributed throughout virtually all cells of the body. The range ofthreats may lead to widespread symptoms. Imposed physical activity isthe wrong thing to be doing as it will likely exacerbate adversesignaling in patients expressing these SNPs.

Acetyl choline is a major neurotransmitter seen throughout the entireperipheral, autonomic and central nervous systems and is also part ofthe non-neuronal signaling mechanisms of the ancient immune system.

SNPs may cause change in protein structure of translated protein andtherefore possibly change in function of these ion channels orreceptors.

280 people were recruited and screened using the CDC criteria andexclusion criteria. 115 had ME/CFS, 90 were non-fatigued and 75 wereexcluded. Those included were given questionnaires (SF36, FSS, KPS),and included housebound patients. Bloods were taken for testing.

13 SNPs were associated with ME/CFS compared to controls (9 – TRPM3, 2– TRPA1, 2 – TRPC4). TRPA1 is activated by exogenous and endogenousinflammatory agents, leading to pain and inflammation.

It regulates neuropeptides and is a multiple chemical receptor. It isassociated with changes in neuropeptide receptors and inflammatorycytokine profiles. TRPM3 is located on the pancreaticβ cells and inthe CNS. It is associated with pain. TRPC4 is associated withvasomotor function and smooth muscle function.

Jo Cambridge (London, UK) then talked about B cell biology and ME/CFS.She gave some background history explaining that Rituximab had beenused in 1998 to treat Rheumatoid Arthritis and SLE. The work of Mellaand Fluge then further drove the hypothesis that B cell depletioncould be implicated in ME/CFS. Her group looked at B Cell biology,biomarkers for response and relapse and other B cell directedtherapies. The B cell has a large number of markers. Markers tell theage of the cell and other expressions. Every new B cell has adifferent receptor. Adherence is involved. B cells move through plasmacells to make antibodies. Antibodies are a form of B cell receptor,and are released onto surfaces, and bind to help clear macrophagesfrom the body. They are made in the bone marrow and circulate tolymphoid organs. Antibodies recognize the different stages on thetarget bug. (e.g. antigen). IgM, IgA, IgG are all a different shape,all recognize the same antigen, but bind to cells in different ways.In a normal immune response, IgM is apparent in the first 7-10 days,then IgG. Memory B cells also form to attack recurrent bugs. There isinteraction with T cells causing cytokines to help B cells make theantigen.

Cytokines interleukin8 and interleukin5 are elevated in ME/CFS andinterleukin23 is down. There are also early and late effects in thisillness leading to different cytokine levels. Antibodies in diseasecan form to "self" giving rise to immune complexes lodging in tissuesleading to inflammation (e.g. lupus, rheumatoid arthritis). Theantibodies bind and damage or change cell function. They can interferewith communication between cells.

Rituximab works in diseases where there are antibodies, leading to Bcell depletion by recognising CD20 on the B cell. This in turn leadsto B cell destruction in the circulation. B cells can regenerate.Changes occur in levels of Anti CCP after a single rituximab course.It is very complicated.

In ME/CFS there were positive results from use of rituximab in Norway.Patients do differ and there is no clear picture of the B cells. The Bcell phenotype can be compared to the ME/CFS demographics using flowcytometry. One can look at complex things such as maturation, plasmacells, percentage of B cells in the blood, associated demographics,percentages of memory and naïve B cells etc.

CD24 is present on B cells associated with maturation (mainly on youngcells). CD38-CD21 – memory B cell subsets – high expression incontrols, less so in ME/CFS. Duration of illness gives differentlevels, with B cells normalizing over time. There are no differencesin classical B cells.

Immune brain communication and relationship to inflammation inducedfatigue were discussed by Neil Harrison (Sussex, UK). He outlined thesymptoms associated with sickness behavior and listed the behaviouralchanges that occur to protect the body. He explained how cytokinesinjected into rodents led to symptoms of sickness behavior. Humansgiven high doses of interferon-αto treat Hepatitis C also developsickness behavior and often experience severe fatigue. There isimmune-brain communication via a number of pathways, and in particularvia the vagus nerve. The microglia are also activated leading to braininflammation.

Typhoid vaccine was used as a bacterial mimic. The fMRI showedactivity++, and PET showed increased metabolism particularly withinimmune-brain communication pathways. Inflammation induced insularactivity, which predicts fatigue. Interferon mediated fatigue is aside effect of interferon-αtherapy (a viral mimic). MRI scans weredone before, and shortly after beginning Interferon-alpha therapy thenpatients followed up for their 6-month duration of treatment. Achallenge with IFN lead to the onset of fatigue and Invest in ME

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MRI changes within 3 hours. One could also use changes observed on MRIto predict which patients would subsequently develop the worst fatigueduring their 24 weeks of treatment. There are implications forpost-IFN fatigue and post viral fatigue. He asked the question "Dostructural brain abnormalities persist post-inflammatory challenge?".

John Chia (California, USA) updated us on his work with enteroviruses.He explained that there are many illnesses associated withenteroviruses. Most doctors are not trained to diagnose enterovirusinfection. They are difficult to recognize. In 1995 41% CFS patientshad positive serum enterovirus. He presented his research up to thepresent. He worked initially with blood samples, but moved onto tissuesamples. In patients with persistent gastrointestinal symptoms, therewas no evidence of H Pylori. But there were positive abdominal tenderpoints, and focal gastritis on endoscopy (often mild).135 out of 165patients were positive for VPI within the parietal cells, compared to7 out of 34 controls. He tried to culture the viruses, but nonesurvived. In 2008, viruses were found in biopsies (Enterovirus capsidprotein) 81% showed VPI and 91% dRNA. Work with SCID mice showedeffects of enterovirus infection after injection. (66% positivecompared to 10% controls). He says that initial infection in thestomach is not controlled by the immune response. Enteroviruses travelvia the vagus to the brainstem.

Claire Hutchinson (Leicester, UK) had looked at visual processing inME. She talked about how visual symptoms were commonly reported in the63 patients studied, using questionnaires and free report of symptoms.She wanted to map anomalous visual behavior onto the visual pathway,and to provide evidence to support symptom reports. There wasexperimental for the existence of visual stress/pattern glare in 20patients compared to controls, which may reflect corticalhyperexcitability. In a study looking at visual attention and theability to ignore background information (29 patients, 29 controls),found basic visual processing speed was normal, but both dividedattention and selective attention were slow. She also presented datashowing that, under some conditions, eye movements are less accuratein people with ME.

Betsy Keller (Ithaca,USA) went through activity guidelines to avoidsymptom flares. This was an active talk incorporating audienceparticipation. She talked about energy currency and post-exertionalmalaise (PEM), describing short term anaerobic, long term anaerobicand aerobic stages (>2 minutes) - the latter not being suitable for aperson with ME/CFS because this energy system fails to recovernormally. She described the abnormal recovery response, with ME/CFSpatients taking 3 days or longer to recover from 5-10 minutes on atreadmill. PEM is the defining quality of this illness. It is easierto avoid it than to recover from it. Her advice is to pre-empt PEMwith scheduled rest periods, do not wait for a crash, pace carefully,know your triggers and avoid or minimize them. Exercise should beredefined with focus on quality of life and use of the short-termenergy systems that do work. Yoga and Tai Chi are suitable forms ofexercise. The strategy for physical activity should use functionalmovement that is restorative, with a goal to improve. Aim should be touse the anaerobic energy systems with a work/rest ratio of 1:3, 1:4 ormore if needed. That is, 'work' for 30 seconds, recover for 90 seconds(1:3).

She went on to explain the importance of core stability to conserveenergy. The core includes muscles, bones, connective tissue of thetrunk from the neck to hips- it connects the extremities. Sheexplained the weight of the head and how it increases if one slouches(using extra energy unnecessarily). Warm up should begin with focused,square or nose-breathing (4 sec inhale, 6-8 exhale). This will oftenhelp symptoms too by better oxygenating the tissues.

5 steps to align core: 1) Contract pelvic floor (contract muscles thatstop flow of urine or Kegel), 2) draw in umbilicus (draw belly buttontoward spine), 3) raise ribcage (rib cage points up toward ceiling orumbrella diaphragm). 4) Lift shoulders up to ears then back and letdrop down, 5) retract chin. (Some of these exercises can be done lyingdown). Back extension is important (lying on floor on belly). She thenran through some exercises on the floor or Swiss ball straighteningarms and legs - alternate and opposite sides. These exercisesstrengthen the core. It is important to assess how one feels the nextday to determine if the work/rest ratio is sufficient. If structuredactivity works, core stability improves, movement Invest in ME

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becomes more efficient and less energy draining. Activities need to bemonitored and modified. The exercises should be very brief e.g. 30seconds of activity, 90 seconds of rest, 3 times. The heart rate (HR)can be monitored and should not exceed the anaerobic threshold, andwatch to see which exercises work at what HR. There is a perceivedexertion scale and the aim should be to stay at the bottom level.

She described structured activity as empowering, improving quality oflife, giving a sense of control and being off the rollercoaster.Energy conservation involves pacing, body position, joint protectionand activity planning. There is need to think circularly not linearly(use a work/rest ratio all day), acknowledge limitations, aim for corestability and structure physical activity. She then outlined 10 simpleenergy-saving tips shared with her by Staci Stevens of the WorkwellFoundation:

Make bed while you are in it or not at allTake things around the house in a back pack.Shower sitting downSimplify clothes and hairUse an answering machinePack groceries smartly ready for unpackingCook aheadGet disabled car parkPrioritize choresLearn to say No and Yes

Olav Mella (Bergen, Norway) brought us up to date discussing the Phase2 and 3 studies of the rituximab trial. The Phase 2 study will bepublished shortly. 20% patients had a transient worsening of symptoms.There was marked improvement of physical function in 6 of 9 previousplacebo patients. Half of the original responders were stillresponding at the end of follow up (36 months). The quality of life ofthe responders was very good. Only 5 patients were as low as 30%.During the trial levels of function were tested using a bicycle on aramp. Experience with measuring endothelial dysfunction was gained.Maintenance therapy may sustain response

A new study is now underway. Patients recruited have been ill for 2-15years. The Canadian criteria were used for diagnosis. 4 universityhospitals and a community hospital were involved. Patients were giveninformation and filled in the De Paul questionnaire. Biobank materialwas withdrawn and frozen. Patients undergoing the ramp test may needto wait 3 months before start of treatment to get back to their normallevel. The study is randomized, double blinded, placebo-controlled.Study period will be 24 months, so results will be available in summer2017, unless there are serious side effects. There will be no accessto randomisation. All monitoring will be external. The physiciansconcerned will not see the patients. Rituximab 500mg/m2 will be givenon days 0 and 15, and then 500mg at 3, 6, 9 and 12 months. Patientswill monitor themselves. SF36 will be used every 3 months and FSS atzero, 6, 12, 18 and 24 months. Electronic activity will be assessed atzero and 18 months, using a wrist band. Blood samples will be drawnregularly for biobank freezing.

The primary endpoint will be the level of fatigue over 24 months. Thesecondary endpoint will be changes in QOL, and any effects oftoxicity.

Sub-studies will include endothelial dysfunction (large vessels -ultrasound and microvessels - PORH analysis) – Is there correlationbetween endothelial dysfunction and ME and improvement parallel toendothelial dysfunction? Ergo spirometry can be used, if patient isable, to see if there are changes in the anaerobic threshold.

Another sub-study will look at gastro-intestinal function. Invest in ME

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These are high quality studies hoping for good clinical response. Onemust expect up to 20% placebo response, and hope for a 50% rituximabresponse. One needs to look at clinical characteristics of theresponders. There may be a 4-5 month delayed response. The biobankwill be useful. There may be political impact. Another multicentertrial elsewhere is needed. Toxicity also needs to be considered. Somepatients cannot tolerate the treatment.

A further new study using cyclophosphamide started in March 2015. Thisis a cheaper immune-modulating drug. It shows major improvement intreatment for breast cancer. 40 ME patients have been recruited with 6infusions to be given every 4 weeks. There are 3 groups of patients:those not treated with rituximab, previous non-responders to rituximaband those who have recurred after rituximab. Patients with mild tomoderate illness are recruited and the trial will last 2 years. Itdoes not include young patients or those at risk of pregnancy. It willbe tried later on for 20 more severe patients.

The conference concluded with thanks to all speakers and closingremarks from Dr Ian Gibson and Invest in ME, and all agreed it hadbeen the very best yet.

I would like to thank Invest in ME and ANZMES for making it possiblefor me to attend this excellent event.

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Chronic fatigue syndrome (CFS) is a devastating illness that caninterfere with all facets of life. It's not clear how many peoplesuffer from CFS, but a recent estimate suggests the number is between836,000 and 2.5 million in the U.S. According to the Centers forDisease Control and Prevention (CDC), women are two to four times aslikely as men to get a diagnosis of this condition. You might also seeCFS called by an older name, myalgic encephalomyelitis (ME), or acombination of the two names (ME/CFS).

Yes, It's "Real"

When we first began hearing about CFS decades ago, many clinicians(doctors, nurse practitioners, physician assistants), and even friendsand relatives of people with CFS questioned whether it was a "realdisease" or "just a mental health condition" or a "figment of theimagination." They had a hard time believing that a condition thatcouldn't be diagnosed with a blood test, x-ray, or physicalexamination could be real. Diagnosis depended (and still depends)solely on what the patient reports.

Recently the Institute of Medicine (IOM) and the National Institutesof Health took a strong stand on CFS. Based on more than 9000 research studies, these organizations concluded that CFS has a biological basis (occurs because of one or more body malfunctions), declaring it "a serious, chronic, complex systemic disease that can profoundly affect the lives of patients." They also stated that CFS is not "a psychological problem."

The studies identified many differences between people with CFS andhealthy people or those with other conditions that cause severefatigue (such as depression or multiple sclerosis). Differences wereidentified in the brain and nervous system, the immune system (whichdefends the body against infection), and the endocrine system (whichregulates body function through glands and hormones). The IOM alsonoted that CFS sometimes occurs following infection with theEpstein-Barr virus and possibly infections with other viruses,bacteria, and protozoa. Learning more about these factors may helpresearcher develop tests for diagnosing CFS, as well as medicationsand other approaches for treating it.

Diagnosing CFS

A diagnosis of CFS still relies on the patient's description ofsymptoms. CFS is identified when what you are experiencing matchesguidelines developed in 1994. According to those guidelines, you haveCFS if, for 6 months, you have had severe, constant, unexplainedfatigue that interferes significantly with daily activities and work,and four or more additional symptoms from a list of eight thatincludes unrefreshing sleep (awakening as tired as you were when youwent to bed) and fatigue made worse by exertion.

The IOM proposed a simpler definition for identifying people with CFS,which may become the new standard. If you fit the criteria listedbelow, if no other cause can be found, and if the problems aremoderate, substantial, or severe and happen frequently (at least halfthe time), the likely diagnosis is CFS:

- A substantial loss of ability to engage in preillness levels ofwork-related, educational, social, or personal activities thatpersists for more than 6 months and is accompanied by fatigue, whichis often profound, is of new or definite onset (not lifelong), is notthe result of ongoing excessive exertion, and is not substantiallyrelieved by rest- Postexertional malaise (worsening of symptoms after physical,cognitive, or emotional activity)- Unrefreshing sleep, PLUS one or both of the following: - Cognitive impairment (trouble remembering, learning new things,concentrating, or making decisions) - Orthostatic intolerance (changes in heart rate and bloodpressure, often resulting in feeling dizzy or lightheaded whenstanding; improving when lying down)

Treating CFS

No specific medication or other treatment can reliably relieve or cure CFS — but since CFS affects lives to such an extent, doing nothing is not acceptable. Treatment is aimed at easing at least some of thesymptoms. For instance, a very low dose of a medication called a"tricyclic" may allow you to get more hours of deep, restorative sleepat night, resulting in more energy the following day. Graded exercisetherapy (supervised physical activity starting at a low level andincreasing gradually) may improve fatigue and function, although itdoesn't help everyone and sometimes causes problems. Counseling,including cognitive behavioral therapy (CBT), may also help. CBT is atherapist-guided method of changing your thinking and fears about yourhealth situation, which may make CFS easier to live with.

The lack of treatment options may make complementary and alternativetreatments, such as acupuncture, massage, and herbal and botanicalproducts, seem attractive. There is little research proving that theseapproaches are safe and helpful, but some women report relief withthem. If you choose to try these options, find out about any possiblenegative effects. Advertising might claim that herbal and botanicalremedies will help you, but the quality, safety, and content of theseproducts is not regulated by the U.S. Food and Drug Administration. Ifyou are considering such a product, check it out at National Centerfor Complementary and Integrative Health (see Resources below). And besure to let your clinician know.

You may also want to consider participating in a research programinvestigating possible treatments for CFS. Places to look for suchprograms include hospitals associated with universities, or the CDCand support groups such as Solve ME/CFS Initiative (see Resourcesbelow).

Coming Soon: A New Name for CFS?

Some experts believe that the term "chronic fatigue syndrome" makeslight of an illness that so profoundly interferes with peoples' lives.Because CFS is a systemic (affecting the whole body) illness marked byexertional intolerance, the IOM proposed a new name that acknowledgesthe true problem: "systemic exertional intolerance disease." That namehas not yet been formally adopted, but you may see it used in thefuture.

In Conclusion

There is still no cure, or even any reliably effective treatment, forCFS. But the IOM report should dispel the myth that CFS is "all inyour head." With more research, more clinician education, and moresupport for those who have CFS, this illness should receive thevalidation and attention it deserves.

For too long the medical community has dismissed 'Chronic FatigueSyndrome' as a mental illness which can be cured with therapy andexercise

By Dr Charles Shepherd9:35AM GMT 07 Dec 2015

Back in 1955, a mysterious polio-like illness affected 262 doctors andnurses at London's Royal Free Hospital. The hospital had to close forjust over three months.

The outbreak was written up in The Lancet and a new neurologicaldisease entered medical language: myalgic encephalomyelitis, or ME, asit still remains in the WHO Classification of Diseases. "Myalgic"referred to the muscle symptoms; "encephalomyelitis" referred to thevarious neurological symptoms.

Others were not convinced that ME was a neurological disease, and twodecades later two psychiatrists, without interviewing any of thepatients, wrote a paper for the British Medical Journal where theyconcluded that the Royal Free outbreak was due to mass hysteria.

The mud from the BMJ stuck. Like most doctors at the time, I leftmedical school believing that ME was not a real disease and I wouldprobably never see a case. I was wrong.

Ignored or dismissed by doctors, people with ME went undiagnosed ormisdiagnosed for long periods of time, often combined with harmfulmanagement advice – as is still the case. I can confirm this afterdeveloping classic ME following chickenpox, caught from one of myhospital patients. Some developed severe ME, becoming housebound orbed-bound with no medical help. Some never recovered.

During the 1980s, ME was redefined and given a dreadful new name:chronic fatigue syndrome (CFS). The term CFS trivialised a seriousmedical condition – the equivalent of trivialising dementia by callingit a chronic forgetfulness syndrome – and shifted the focus from a"disease" to a single symptom, "chronic fatigue".

CFS also brought in a much wider group of people suffering fromchronic undiagnosed fatigue. A powerful body of psychiatric opinionconvinced the medical profession that CFS was basically a mentalhealth problem whereby people became trapped in a vicious circle ofabnormal illness beliefs and behaviours, inactivity anddeconditioning. In other words, there was no "disease" present.

The CFS model of causation resulted in two controversial forms ofbehavioural management – cognitive behaviour therapy (CBT) and gradedexercise therapy (GET) – being recommended by NICE as the main form oftreatment.

Now we have the PACE trial – the largest and most recent assessment ofCBT and GET, which has cost the taxpayer almost £5 million. At longterm follow-up, and contrary to what was reported in the press, thePACE trial found no significant difference between CBT, GET, adaptivepacing and specialised medical care.

Public reaction to the spin that has been put on the PACE trialresults for CBT and GET has resulted in over 10,000 people signing apetition calling for claims relating to so-called recovery to beretracted and six academic researchers calling for an independentreview of the study.

By contrast, in evidence collected from 1,428 people with ME by the MEAssociation, for which I am medical adviser, 73 per cent reported thatCBT had no effect on symptoms while 74 per cent said reported that GEThad made their condition worse. The MEA has therefore recommended thatNICE withdraws their advice relating to GET.

On the progressive side of this medical divide are physicians andresearchers who, like the patient community, believe that ME is aserious multi-system disease, often triggered by infection, butmaintained by abnormalities involving, neurology, muscle, and theimmune system.

In the UK, a research collaborative with a strong emphasis on thebiomedical research has been established. And a major report from theprestigious US Institute of Medicine has recently concluded that ME isa "serious, chronic, complex, systemic disease that can profoundlyaffect the lives of patients". ME is not a psychological problem.

Biomedical research into ME is revealing abnormalities in the way thatmuscle creates energy, along with evidence of an ongoing overactiveimmune system response. New types of brain imaging are demonstratinglow-level inflammation in several specific parts of the brain.

At the same time, a large multi-centre clinical trial is taking placeto assess the use of Rituximab – a drug that depletes immune system Bcells and which is normally used to treat a form of cancer calledlymphoma.

The argument here is not with mental illness, which is just as realand horrible as physical illness. As with any long-term illness, somepeople will develop mental health problems where talking therapies canclearly be of help.

The argument is with a simplistic and seriously flawed model ofcausation that patients know is wrong and which has seriously delayedprogress in understanding the underlying cause of ME and developingeffective forms of treatment.

Opening the 2015 research collaborative section of neuropathology,Jose Montoya, professor of medicine at the University of Stanford,said: "I have a wish and a dream that medical and scientific societieswill apologise to their ME patients."

I agree – the time has come for doctors and scientists to apologisefor the very neglectful way in which ME has been researched andtreated over the past 60 years. Doctors need to start listening totheir patients and there must now be increased investment inbiomedical research to gain a better understanding of the diseaseprocess and to develop treatments that these patients desperatelyneed.

Dr Charles Shepherd is medical adviser to the ME Association

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Fact box

Symptoms of Chronic Fatigue Syndrome

The main symptom of CFS is persistent physical and mental fatigue(exhaustion). This does not go away with sleep or rest and limits yourusual activities.

Most people with CFS describe this fatigue as overwhelming, and adifferent type of tiredness from what they have experienced before.

Other symptoms include:

- Muscular pain, joint pain and severe headaches- Poor short-term memory and concentration, and difficulty organisingthoughts and finding the right words ('brain fog')- Painful lymph nodes (small glands of the immune system)- Stomach pain and other problems similar to irritable bowelsyndrome, such as bloating, constipation, diarrhoea and nausea- Sore throat- Sleeping problems, such as insomnia and feeling that sleep is not refreshing -Sensitivity or intolerance to light, loud noise, alcohol and certain foods

Thursday, November 19, 2015

Journalist David Tuller writes about how he became interested in Chronic Fatigue Syndrome and what brought him to write so much about the PACE Trial (the largest CFS trial ever)http://linkis.com/alumni.berkeley.edu/pYqqm

Monday, November 16, 2015

"After a battery of diagnostic tests for viruses and bacteria, [Montoya] continued Cavanagh Kramer on one of the antivirals she'd been prescribed, but made a few important changes: He added anti-inflammatory and immune-modulating drugs, as well as an antibiotic for the bacteria he found in her blood. ... Historically, many doctors considered CFS a psychosomatic disorder that required psychological—not medical—intervention. But recent research by Montoya and others has compelled the medical community to take the condition much more seriously. ... Montoya and his colleagues, however, were able to pinpoint immune abnormalities in the blood of CFS patients who had recently become ill, suggesting possible biomarkers for the disease. ... A picture of patients with highly inflamed bodies emerged before our eyes and validated what they've been telling us for decades."

Darcy Olsen is President of the Goldwater Institute, a research and legal center, which is currently behind the Right to Try initiative, to give terminally-ill patients access to medications before the FDA approves them.

I saw her on TV this morning. She asked pointedly why drugs which are available in Europe are not FDA-approved for use in the US. Apparently Right to Try would allow Americans to use anything that's approved elsewhere.

Ampligen has been used in both Belgium and Canada, but in the US, FDA just keeps asking for more testing.

Could that possibly be because Dr. Reeves and Dr. Straus so vehemently insisted that CFS is all in our heads, and it wouldn't be politic for FDA to approve an anti-viral drug for something CDC says is purely psychiatric?

Unfortunately, the magic words in the proposed legislation are "terminally ill" and I don't think anyone classifies ME/CFS as "terminally ill".

"you can't talk someone out of a delusion. That's the definition of delusion. It is a belief in the face of contrary evidence."

* * *

A lot of people (doctors and psychobabblers included) think this is our problem -- that we don't want to admit that we have a mental illness and are clinging to the delusion that we are physically ill, and therefore need to be medicated without consent for whatever erroneous amateur psych diagnosis that particular doctor likes best (I've been tagged with anxiety and depression, while psych experts have never found signs of either). Doctors dismissed those psych reports and wanted me to go see another shrink, one who might agree with them.

But the reality is, it's those psychobabblers who have the problem. "You can't talk someone out of a delusion. That's the definition of delusion. It is a belief in the face of contrary evidence." Shown evidence of physical illness (abnormal temperature, swollen glands, abnormal test results), they will continue to insist that there is nothing physically wrong with you. At one appointment, my temperature was 95 -- hypothermia -- which did not disturb the doctor as much as it should have, because he refused to accept any contrary evidence. When confronted, he shrugged, "you were outside". Yes, I was outside for a few minutes in the sun on a 60-degree day, but that wouldn't push my temperature down to 95. He wanted to see a depressed divorcee too lazy to work, and was willing to dismiss any symptoms or evidence that there was more to it than that. He was delusional, and in order to continue his delusion, he had to convince me that I was delusional in thinking that I was physically ill. He couldn't do any tests that might prove I was right and he was wrong, so he simply refused to order those tests.

Tuesday, November 10, 2015

"TVAM is a treatment involving the endovenous stimulation of autonomic nerve fibers via a minimally invasive procedure. The process of manual stimulation of these nerve fibers appears to have a modulatory effect on the autonomic nervous system."

The full text about the XMRV-fraud and CFS is available online,Chapter: Science as as Social ProcessSection: Correction of Faulty Results after PublicationPages: 219-226URL: http://books.google.com/?id=CHDbBgAAQBAJ&pg=PA219

"Until recently, the Centers for Disease Control and Prevention has emphasized the psychosomatic hypothesis in their research on CFS, although several scientists have looked for associations between CFS and infection with various viruses."

Then there's a description of the XMRV fiasco. "This outcome doesn't mean absolute refutation of the hypothesis that CFS is caused by an infectious agent -- another virus or even another type of infectious agent could be responsible for the disease. ... the research that followed Mikovits's study and culminated in Lipkin's project has spurred greater scientific attention to CFS and may stimulate more research on various hypotheses about causes of the disease."

* * *

The good news is that students are now being taught the possibility that CFS is not just all in our heads, but caused by a virus.

Unfortunately, the whole XMRV mess is exposed to a wider audience in a way that could scare students off getting involved in controversial research like CFS. Since this is a book about "critical thinking", it was a good description of something that was disproved by critical thinking (trying to replicate research and not just accepting it as true based on one study), so there is some benefit to it if you turn it on its head, the studies claiming IAIYH also cannot be replicated when using real CFS patients rather than "tired all the time" depressives.

Saturday, November 7, 2015

If they can do it for poliomyelitis, why not for myalgic encephalomyelitis? The ability is there, just the specific research is missing.

In polio epidemics, they found that those who had ME/CFS were immune to polio, therefore, they have to be related viruses. Dr. Bruno tells me the polio vaccine prevents the three worst forms of the virus, leaving lesser mutations unguarded against. Including the relative that causes ME/CFS.

Because of the aggressive campaign, it's expected that the last cases of polio seen in the wild will happen sometime in the next two to three years. The World Health Organization is so confident about this that it actually has what's calledthe Polio Eradication and Endgame Strategic Plan, a strategy on how to make the world polio-free by 2018.

That's extraordinary. This has only happened once before in history,when smallpox was eliminated in 1977. Smallpox killedhundreds of millions of people, and now it's gone, wiped clean off the face of the planet.

Why? Again: vaccines.

This is why I consider vaccines to be one of the very best medical health innovations in human history, if not the best.

Wednesday, November 4, 2015

Over the past year, I've been invited to a few sessions about the problem that the disabled don't vote. The able-bodied people in government can't figure out the problem themselves.

If we don't vote, that means we're not voting out politicians who want to cut Disability checks and services to the disabled. Yes, thousands of us show up on the front lawn of the State Capitol every year for Disability Capitol Action Day, to prove to the legislators (who are used to seeing us in onesie-twosies representing individual diseases) that the disabled as a whole are a large voting bloc. But are we really? How much of a voice do we have if many of us don't actually vote?

One of the issues brought up repeatedly was inability to get to the polls. We don't drive or we can't afford a car. My local polling place was moved from across the street to a building several blocks away where I would actually have to walk further to take the bus than I would to walk there directly. Out in rural areas, it's even worse -- no buses at all.

Yes, you can vote by mail (and for the homebound, that's the only option). But charities and clubs could provide free rides to the polls if they realized there's a need. Call some in your local area and suggest it.

Check with your local voter registration office whether you can register as a Permanent Absentee Voter, so you will always get your ballot by mail, or whether your local law requires you to request an absentee ballot each time. Then once you have the ballot, make sure you mail it back in plenty of time to be counted. Sign the back of the envelope to prove you're you. Put enough stamps on it. If you can't get out to put it in the corner mailbox, hand it to the mail carrier and ask him to take it to the post office for you.

In my state, a few weeks before an election, we're sent a booklet with the full text of all the propositions, brief candidate statements, and a sample ballot. You can take your time going through it, use a highlighter to mark up the sample ballot, and then when you have your real ballot (whether vote by mail or at the polls), it's a simple matter to just transfer your choices from the sample ballot to the actual ballot. You don't have to strain to read the fine print while you're at the polls. This information is often available online, for those who use a screenreader or need to increase the size of the print.

Did you know that there are now computerized voting machines for the disabled? Bring your own headphones, and your own puff straw if you're paralyzed, and cast your secret ballot. But you may need to know that it's there, because the pollworkers may not know they have such a machine tucked off in the back corner, and you may need to know how to use it, because the pollworkers may not know enough to teach you. At the Secretary of State's workshop, we were each given a one-on-one demo specific to our own disability, but they wouldn't let us bring one home so we could teach others, so all I can teach you is to ask if there's a machine available. Again, you'll have to call your own state's Secretary of State or county Registrar of Voters to find out if these are available and if they can show you how to use it. Maybe they'll bring one to your next support group meeting. Don't wait till just before the election when they're busy with preparations -- invite them for a few months before when they have time.

If the pollworkers are helpful, send an e-mail to the Registrar of Voters to thank them. If the pollworkers are rude because of your disability, send an e-mail to the Registrar of Voters explaining the problem and requesting sensitivity training.

Don't think that politics is boring -- politics is what decides whether we get a cost of living increase (which we won't for 2016) or a 20% benefits cut (which was threatened) combined with a huge increase in Medicare premiums (they were threatening to increase it 50% while simultaneously reducing benefits by 1/5). Politics determines everything about how the disabled are treated.

You don't need a lot of money to have an impact on politics -- it costs nothing to go to a campaign office to volunteer your time (and you'll often get fed while you're there), and almost nothing to get a campaign button/bumper sticker (sometimes free, sometimes a dollar or two), T-shirt (a few dollars), or lawn sign (I paid $10 for the last one, and they installed it for me).

You can call their offices for free. You can e-mail their offices for free. We may not have a lot of money, but we do have time.

And you can vote out the people who threaten to reduce our benefits and services, refuse to enact expanded Medicaid for the working poor (which is a lot of the disabled), or any of the other things that politicians like to do in hopes the disabled will just go away.